ABSTRACT Adolescence marks a key period in the development of problematic alcohol use, with approximately 15% of 18 year olds meeting criteria for alcohol use disorder (AUD). Efforts to treat adolescent AUD have been only modestly effective, with up to 86% of youth returning to use within 12 months following treatment. Inadequate treatment for adolescents is an important public health concern given that alcohol use during this time is highly predictive of long-term problematic drinking. While several medications are efficacious in treating adult AUD, minimal pharmacotherapy research has focused on adolescents. Evaluation of alternative and more efficacious treatments for adolescents with AUD is warranted. The primary objective of the proposed Phase II proof-of- concept study is to evaluate the effect of N-acetylcysteine ( NAC), compared to placebo, in reducing alcohol use among treatment-seeking adolescents with AUD (N=120). Given NAC?s effect on addictive behaviors via glutamate modulation, accessibility as an over-the-counter supplement, safety and tolerability with adolescents, and low cost, this medication holds great promise as a potential treatment option for adolescents with AUD. In response to the National Institute on Alcohol Abuse and Alcoholism?s initiative to accelerate research on the development of effective pharmacologic treatments for AUD, we will (1) conduct an 8-week, intent-to-treat, double-blind, parallel-group, randomized, placebo-controlled trial of NAC (2400 mg per day); (2) examine standardized, repeated dependent measures of clinical outcomes at baseline, throughout treatment, and at post- treatment follow-up; and (3) employ mobile technology to improve data collection, engagement, and medication adherence. The identification of a well-tolerated, effective pharmacological treatment would represent a significant advance and could yield tremendous public health impact. The proposed trial will provide critical data to evaluate NAC as a pharmacotherapy for adolescent AUD, and regardless of NAC versus placebo outcomes will provide key methodological guidance for future randomized controlled trials of pharmacotherapies for adolescent AUD.